Engineering galactoside acetyltransferase for enhanced hesperetin-7-O-glucoside bioavailability.

ABSTRACT: Flavonoid glycosides exhibit compromised bioavailability due to low membrane permeability. To address this limitation, we acetylated flavonoids through enzymatic reactions to increase bioavailability. This study first reported that Hesperetin-7-O-glucoside (Hes-7-G) was acetylated by galactoside acetyltransferase (GAT), and the apparent permeability (P_app) of the Caco-2 monolayer was increased by 69%, indicating the acetylated Hes-7-G application potential to improve bioavailability. Subsequently, we designed GAT mutants through comprehensive computational and experimental methods to improve the acetylation efficiency and elucidate the catalytic mechanism. Molecular Dynamics (MD) simulations found that Tyr483 and Met127 are key residues that control flavonoid binding through dyn

SUBMITTER: Wang JX 

PROVIDER: S-EPMC12775004 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature